The patch clamp will be used to record single channel currents coupled to the GABA receptor of mouse spinal cord cell cultures. Data produced by GABA and by the GABA agonists muscimol and pentobarbital will be analyzed by a number of procedures designed to characterize the channel gating mechanism. This basic molecular information will then be used as a framework for the study of the mechanism by which barbiturates and benzodiazepines potentiate the GABA response. Different physiological responses to GABA have previously been identified. An attempt will be made to reduce the observed cellular responses to differences at the level of channel currents, and thereby obtain a biophysical basis for multiple GABA responses. Diversity in the properties of the GABA receptor channel will then be explored in cultures grown under conditions where spontaneous electrical activity is blocked, or where electrical activity is paroxysmal. In response to conditioning by pharmacological treatments which produce altered patterns of electrical activity, neurons may produce GABA receptor channels with different unitary properties and different physiological functions.